Novel biomarker for evaluation of autophagic dysfunction in the liver

• Project/Area Number: 23590989
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Juntendo University
• Principal Investigator: YAMASHINA SHUNHEI 順天堂大学, 医学部, 准教授 (30338412)
• Co-Investigator(Kenkyū-buntansha): UENO Takashi 順天堂大学, 医学研究科, 教授 (10053373) ; IKEJIMA Kenichi 順天堂大学, 消化器内科, 准教授 (20317382)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: オートファジー / バイオマーカー / 核膜蛋白 / 肝疾患

Research Abstract

We found that autophagic dysfunction alters the expression of nuclear membrane protein. Nuclear membrane proteins increased in autophagic dysfunction might be an useful biomarker to evaluate autophagic dysfunction. On the other hand, aggregation of p62 in hepatocytes was detected in about 65% of NAFLD correlatively to suppression of cathepsin B, D and L expression. In NAFLD patients, p62 aggregation was correlated with serum alanine aminotransferase value and inflammatory activity by NAS. These findings indicate that the suppression of autophagic proteolysis by hepatic steatosis is involved in the pathogenesis of NAFLD.

Research Products

• [Journal Article] Abnormality of autophagic function and cathepsin expression in the liver from patients with non-alcoholic fatty liver disease. (2014)
  • Author(s): Yuka Fukuo, Shunhei Yamashina, Hiroshi Sonoue, Atsushi Arakawa, Eisuke Nakadera, Tomonori Aoyama, Akira Uchiyama, Kazuyoshi Kon, Kenichi Ikejima, Sumio Watanabe
  • Journal Title: Hepatology Research Volume: 未定 Issue: 9 Pages: 1026-1036
  • DOI: 10.1111/hepr.12282
  • Peer Reviewed / Open Access
• [Presentation] 非アルコール性脂肪性肝疾患患者におけるオートファジー機能障害とカテプシン発現異常 (2013)
  • Author(s): 福生有華,山科俊平,泉光輔,園上浩司,荒川敦,青山友則,内山明,今一義,鈴木聡子,池嶋健一,渡辺純夫
  • Organizer: 肝臓(0451-4203)54巻Suppl.1 PageA146
• [Presentation] NAFLD患者における肝カテプシンL発現とオートファジー機能の評価福生有華 (2012)
  • Author(s): 山科俊平,泉光輔,稲見義宏,山形寿文,今一義,鈴木聡子,池嶋健一,渡辺純夫
  • Organizer: 肝臓(0451-4203)53巻Suppl.3 PageA929